A paucity of liver disease in Canadian Inuit with chronic hepatitis B virus, subgenotype B6 infection.

Clinical observations suggest that chronic hepatitis B virus (HBV) infections in the Canadian Inuit are less often associated with serious adverse outcomes than has been described in other HBV-infected patient populations. The aim of this study was to document the clinical and biochemical features, liver-related morbidity and all-cause mortality in Canadian Inuit with chronic HBV infections. Administrative databases were reviewed for individuals identified as hepatitis B surface antigen (HBsAg) positive during a 1983-85 seroepidemiological survey of viral hepatitis in Baffin Island, Canada. An equal number of age- and gender-matched HBsAg-negative individuals from the same communities served as controls. Baseline HBV viral loads, genotypes and specific mutations were compared in HBsAg-positive survivors and nonsurvivors. A subset of surviving HBsAg-positive carriers were reassessed 25-30 years following their initial diagnosis for evidence of advanced liver disease and changes to their serological/virological findings. One hundred and forty four HBsAg-positive individuals were identified. All were Canadian Inuit. The mean age at diagnosis was 38 ± 17 years and 69 (61%) were male. Median follow-up was 23 years (range: 2-28 years). Viral quantitation from stored sera could be performed in 70 infected individuals. The median viral load was 4.3 log 10 IU/ml (range: 2.3-8.8 log 10 IU/ml), and all were genotype B, subgenotype B6. Liver biochemistry, morbidity and all-cause mortality rates were similar in HBsAg-positive carriers and controls. Following multivariate analyses, only age at diagnosis predicted mortality in HBsAg carriers. In a subset of 30 HBsAg-positive survivors who underwent follow-up assessments, clinical, biochemical and radiological examinations of the liver were essentially normal. 23/30 (77%) remained HBsAg positive and 17/19 (90%) HBV-DNA positive. The genotype and prevalence of genomic mutations in this cohort remained largely unchanged, but quantifiable viral loads were significantly lower (P < 0.003). The results of this study suggest that chronic HBV infections in the Canadian Inuit are infrequently associated with serious adverse outcomes. Whether this finding reflects unique features of the host, presence or absence of external factors that influence the course of HBV and/or intrinsic properties of the HBV B6 subgenotype remains to be determined.

The prevalence and long term outcome of occult hepatitis B virus infections in community based populations.

Features of occult hepatitis B infection in community-based populations have yet to be described. In this study we documented: (1) the prevalence and demographics, (2) associated serology and viral loads, and (3) clinical outcomes of occult hepatitis B infection in community-based populations. Hepatitis B surface antigen (HBsAg)-negative sera collected from three Northern Canadian communities (HBsAg prevalences: 11-12%) in 1983-1985 were tested for HBV-DNA by nested stage polymerase chain reaction. Of 706 HBsAg negative sera, 9 (1.3%) were HBV-DNA positive. The median age of occult hepatitis B infected patients at the time of sampling was 9.8 years (range 3.1-50.4 years) and six (67%) were female. Two (22%) individuals were anti-HBs positive (in the absence of prior vaccination). Viral loads were undetectable in all but two samples (2.40 and 2.86 log10 IU/ml). Only one of the five (20%) patients who were assessed clinically, remained HBV-DNA positive at 25-30 year follow-up. There was no clinical, biochemical or radiologic evidence of chronic hepatitis, cirrhosis or hepatocellular carcinoma in these individuals or on review of the charts from the remaining four infected patients. The results of this study suggest that in community-based populations: (1) occult hepatitis B infection is not as common as HBsAg positive infection, (2) the majority of infected subjects are young females, (3) a minority are anti-HBs positive, (4) viral loads are either undetectable or low, and (5) in the absence of concurrent liver disease, occult hepatitis B infection does not appear to be associated with long term adverse clinical outcomes.

Distinct geographical and demographic distribution of hepatitis B virus genotypes in the Canadian Arctic as revealed through an extensive molecular epidemiological survey.

Very little is known of hepatitis B virus (HBV) in Canadian Arctic indigenous populations, where HBV was considered endemic prior to the introduction of HBV vaccine. This study expands upon an HBV seroepidemiological survey conducted between 1983 and 1985 throughout the Canadian Arctic, to characterize HBV in this population. Archived hepatitis B surface antigen (HBsAg)-positive sera (n = 401) were processed for HBV DNA, followed by sequencing and phylogenetic analysis of the HBsAg- and HBcAg-coding regions. Sixty-nine per cent of samples (277/401) were DNA positive, with most having low viral load (median 3.4 log 10 IU/mL). The predominant HBV genotype observed was genotype B (HBV/B, 75%), followed by HBV/D (24%) and HBV/A (1%). All HBV/B strains clustered within subgenotype B6, a newly recognized HBV genotype among western circumpolar Inuit and Alaska Native people. HBV/D strains included both D3 (88%) and D4 (12%) subgenotypes, while all HBV/A strains were subgenotype A2. An association of HBV genotype B with Inuit living in the eastern Arctic and an association of genotype D with First Nation (Dene) living in the western Arctic was observed. This study establishes the high prevalence of HBV/B6 and HBV/D genotypes in Arctic populations and reveals their marked distribution within the Canadian Arctic based on geographical and demographic attributes.

Serological evidence of hepatitis E virus infection in an indigenous North American population.

BACKGROUND: Hepatitis E virus (HEV) infections are thought to be uncommon in North America. Recently, HEV transmission has been reported following the consumption of deer meat. Because deer are closely related to caribou and caribou meat is a staple of the Canadian Inuit and the American Eskimo diet, the present study explored the seroprevalence of HEV infection in an isolated Canadian Inuit community. METHODS: Stored sera were thawed and tested for immunoglobulin (Ig) G and IgM anti-HEV by ELISA, and tested for HEV-RNA by reverse transcriptase polymerase chain reaction. RESULTS: The study consisted of 393 sera (representing approximately 50% of the community's inhabitants). Eleven samples (3%) were IgG anti-HEV-positive. Their mean age was 29+/-8 years and three were male. Two of 11 (18%) were also IgM anti-HEV-positive. All IgG anti-HEV-positive individuals were HEV-RNA-negative. Liver biochemistry was normal in all. Seven of 11 (64%) were also positive for anti-hepatitis A virus, five (46%) were hepatitis B virus seropositive and none (0%) were positive for anti-hepatitis C virus. There were no associations between infections with HEV and other hepatropic viruses. Serological testing was negative for HEV infection in 25 caribou from an adjacent region. CONCLUSION: The results of the present study showed that serological evidence of HEV infection was present in 3% of the observed Canadian Inuit population; the presence of IgM anti-HEV suggested recent infection and HEV did not appear to coinfect with other common hepatotropic viruses. The source of HEV infection in the population remains unclear. These findings are interesting but preliminary. Additional data are required to determine whether HEV infections are responsible for otherwise unexplained acute hepatitis in the Canadian Inuit population and visitors returning from northern North American communities.

HIV-2 in rhesus monkeys: serological, virological and clinical results.

Diseases induced by animal retroviruses are not considered to be good models for the human acquired immunodeficiency syndrome (AIDS) at present. The lack of an animal model for the human immunodeficiency virus (HIV) infection presents a main problem in the complete understanding of the pathogenesis of HIV-mediated diseases. Because of the homologies between simian immunodeficiency virus (SIV) and HIV-2, we inoculated rhesus monkeys with HIV-2 and HIV-2 adapted in vitro to monkey cells. One of the ten animals inoculated developed clinical symptoms that might be related to the infection with HIV-2.

Transmission of hepatitis B by a human bite: an occupational hazard.

Hepatitis B developed in a policeman 15 weeks after he was bitten on the hand. A few days after the bite hepatitis B developed in the assailant. The bite had drawn blood and this method of inoculation was presumed to be the route of transmission of the virus. Compensation was awarded on the grounds that this was an occupationally acquired disease.